The dorsal hippocampus of the rat normally receives its 5-HT innervation from two homologous groups of cells in the median raphe nucleus via the cingulum bundle-induseum griseum (CB-IG) and the fornix-fimbria (FF) (J. Comp. Neurol., 179 (1978) 641-667 and Brain Res. Bull., 10 (1983) 445-451). 5-HT immunoreactive (IR) fibers are distributed in a laminar pattern in the hippocampus. These fibers have large varicosities and are densely distributed in the infragranular layer of dentate gyrus, in the stratum lacunosum-moleculare of the cornu Ammonis and in the area fasciola cinerea (FC). The present study provides evidence that the density of the 5-HT-IR fibers in the dorsal hippocampus is greatly decreased but maintained a similar laminar pattern 3 days after lesioning by microinjection of 4 micrograms of 5,7-dihydroxytryptamine (5,7-DHT) into the CB-IG. An apparently normal density and distribution pattern of the 5-HT-IR fiber is seen by 42 days postlesion. The FC in the hippocampus is among the first regions reinnervated by 5-HT-IR fibers with very dense and large varicosities. The restitution of 5-HT-IR fibers in the dorsal hippocampus after the 5,7-DHT lesion in the CB-IG is accompanied by a marked increase in the number and intensity of 5-HT-IR fibers in the FF. No evidence of a regeneration of 5-HT-IR fibers is seen distal to the injection site in the CB-IG. These observations provide direct evidence for homotypic collateral sprouting in the CNS induced by removal of a single fiber type.